US9961897B2 - Fungicidal pyrazoles - Google Patents

Fungicidal pyrazoles Download PDF

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US9961897B2
US9961897B2 US14/913,509 US201414913509A US9961897B2 US 9961897 B2 US9961897 B2 US 9961897B2 US 201414913509 A US201414913509 A US 201414913509A US 9961897 B2 US9961897 B2 US 9961897B2
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independently selected
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US20160212998A1 (en
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Andrew Edmund Taggi
James Francis Bereznak
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FMC Corp
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EI Du Pont de Nemours and Co
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention relates to certain pyrazoles, their N-oxides, salts and compositions, and methods of their use as fungicides.
  • This invention is directed to compounds of Formula 1 (including all stereoisomers), N-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
  • R 4 is H, amino, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 cycloalkyl, —CH( ⁇ O), —S( ⁇ O) 2 OM, —S( ⁇ O) m R 15 , —(C ⁇ Z)R 16 or OR 17 ; or C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, each optionally substituted with up to 2 substituents independently selected from R 18 ;
  • this invention pertains to a compound selected from compounds of Formula 1 (including all stereoisomers) and N-oxides and salts thereof.
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising (a) a compound of the invention (i.e. in a fungicidally effective amount); and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising (a) a compound of the invention; and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).
  • This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).
  • This invention also relates to a composition
  • a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.
  • compositions comprising, “comprising”, “includes”, “including”, “has”, “having”, “contains”, “containing”, “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated.
  • a composition, mixture, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.
  • transitional phrase “consisting essentially of” is used to define a composition, method or apparatus that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention.
  • the term “consisting essentially of” occupies a middle ground between “comprising” and “consisting of”.
  • plant includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds).
  • Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
  • seedling used either alone or in a combination of words means a young plant developing from the embryo of a seed.
  • narrowleaf used either alone or in words such as “broadleaf crop” means dicot or dicotyledon, a term used to describe a group of angiosperms characterized by embryos having two cotyledons.
  • alkylating agent refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to a leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom.
  • alkylating agent or “alkylating reagent” does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified, for example, for R 1 and R 2 .
  • a molecular fragment i.e. radical
  • a series of atom symbols e.g., C, H, N, O and S
  • the point or points of attachment may be explicitly indicated by a hyphen (“-”).
  • —SCN indicates that the point of attachment is the sulfur atom (i.e. thiocyanato, not isothiocyanato).
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl such as methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers.
  • Alkenyl includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.
  • Alkenyl also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl.
  • Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
  • Alkynyl also includes moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • Alkylene denotes a straight-chain or branched alkanediyl.
  • alkylene examples include CH 2 , CH 2 CH 2 , CH(CH 3 ), CH 2 CH 2 CH 2 , CH 2 CH(CH 3 ), and the different butylene, pentylene or hexylene isomers.
  • Alkenylene denotes a straight-chain or branched alkenediyl containing one olefinic bond. Examples of “alkenylene” include CH ⁇ CH, CH 2 CH ⁇ CH and CH ⁇ C(CH 3 ).
  • Alkynylene denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of “alkynylene” include CH 2 C ⁇ C, C ⁇ CCH 2 , and the different butynylene, pentynylene or hexynylene isomers.
  • Alkylamino includes an NH radical substituted with straight-chain or branched alkyl.
  • alkylamino include CH 3 CH 2 NH, CH 3 CH 2 CH 2 NH and (CH 3 ) 2 CHNH.
  • dialkylamino include (CH 3 ) 2 N, (CH 3 CH 2 ) 2 N and CH 3 CH 2 (CH 3 )N.
  • Alkylaminoalkyl denotes alkylamino substitution on alkyl.
  • alkylaminoalkyl include CH 3 NHCH 2 , CH 3 NHCH 2 CH 2 and CH 3 CH 2 NHCH 2 .
  • dialkylaminoalkyl include (CH 3 ) 2 NCH 2 , CH 3 CH 2 (CH 3 )NCH 2 and (CH 3 ) 2 NCH 2 CH 2 .
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, i-propyloxy and the different butoxy, pentoxy and hexyloxy isomers.
  • Alkoxyalkyl denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • Alkenyloxy includes straight-chain or branched alkenyl attached to and linked through an oxygen atom.
  • alkenyloxy examples include H 2 C ⁇ CHCH 2 O, (CH 3 ) 2 C ⁇ CHCH 2 O, CH 3 CH ⁇ CHCH 2 O, CH 3 CH ⁇ C(CH 3 )CH 2 O and H 2 C ⁇ CHCH 2 CH 2 O.
  • Alkynyloxy includes straight-chain or branched alkynyl attached to and linked through an oxygen atom. Examples of “alkynyloxy” include HC ⁇ CCH 2 O, CH 3 C ⁇ CCH 2 O and CH 3 C ⁇ CCH 2 CH 2 O.
  • alkylsulfonyloxy denotes alkylsulfonyl attached to and linked through an oxygen atom.
  • alkylsulfonyloxy examples include CH 3 S( ⁇ O) 2 O, CH 3 CH 2 S( ⁇ O) 2 O, CH 3 CH 2 CH 2 S( ⁇ O) 2 O and (CH 3 ) 2 CHS( ⁇ O) 2 O.
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio isomers.
  • Alkylthioalkyl denotes alkylthio substitution on alkyl. Examples of “alkylthioalkyl” include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 .
  • Alkylsulfinyl includes both enantiomers of an alkylsulfinyl group.
  • alkylsulfinyl examples include CH 3 S( ⁇ O), CH 3 CH 2 S( ⁇ O), CH 3 CH 2 CH 2 S( ⁇ O) and (CH 3 ) 2 CHS( ⁇ O).
  • alkylsulfonyl examples include CH 3 S( ⁇ O) 2 , CH 3 CH 2 S( ⁇ O) 2 , CH 3 CH 2 CH 2 S( ⁇ O) 2 and (CH 3 ) 2 CHS( ⁇ O) 2 .
  • cycloalkyl denotes a saturated carbocyclic ring consisting of between 3 to 8 carbon atoms linked to one another by single bonds.
  • examples of “cycloalkyl” include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • cycloalkylalkyl denotes cycloalkyl substitution on an alkyl group.
  • examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.
  • Alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety. Examples include 4-methylcyclohexyl and 3-ethylcyclopentyl.
  • cycloalkylcycloalkyl denotes cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 6 carbon atom ring members.
  • cycloalkylcycloalkyl examples include cyclopropylcyclopropyl (such as 1,1′-bicyclopropyl-1-yl, 1,1′-bicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4-cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as 1,1′-bicyclohexyl-1-yl), and the different cis- and trans-cycloalkylcycloalkyl isomers, (such as (1R,2S)-1,1′-bicyclopropyl-2-yl and (1R,2R)-1,1′-bicyclopropyl-2-yl).
  • cyclopropylcyclopropyl such as 1,1′-bicyclopropyl-1-yl, 1,1′-bicyclopropyl-2-yl
  • cyclohexylcyclopentyl such as 4-cyclopenty
  • cycloalkoxy denotes cycloalkyl attached to and linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy.
  • Cycloalkylalkoxy denotes cycloalkyl substitution on an alkoxy group. Examples of “cycloalkylalkoxy” include cyclopropylmethoxy, cyclopentylethoxy, and other cycloalkyl moieties bonded to straight-chain or branched alkoxy groups.
  • Cycloalkylcarbonyl denotes cycloalkyl bonded to a C( ⁇ O) group including, for example, cyclopropylcarbonyl and cyclopentylcarbonyl.
  • cycloalkoxycarbonyl means cycloalkoxy bonded to a C( ⁇ O) group, for example, cyclopropyloxycarbonyl and cyclopentyloxycarbonyl.
  • cycloalkylene denotes a cycloalkanediyl ring. Examples of “cycloalkylene” include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene.
  • cycloalkenylene denotes a cycloalkenediyl ring containing one olefinic bond. Examples of“cycloalkenylene” include cyclopropenylene and cyclopentenylene.
  • Cyanoalkyl denotes an alkyl group substituted with one cyano group.
  • Examples of “cyanoalkyl” include NCCH 2 , NCCH 2 CH 2 and CH 3 CH(CN)CH 2 .
  • “Hydroxyalkyl” denotes an alkyl group substituted with one hydroxy group. Examples of “hydroxyalkyl” include HOCH 2 , HOCH 2 CH 2 and CH 3 CH 2 (OH)CH.
  • Nonroalkyl denotes an alkyl group substituted with one nitro group. Examples of “nitroalkyl” include NO 2 CH 2 and NO 2 CH 2 CH 2 .
  • Alkylcarbonyl denotes a straight-chain or branched alkyl group bonded to a C( ⁇ O) moiety.
  • alkylcarbonyl include CH 3 C( ⁇ O), CH 3 CH 2 CH 2 C( ⁇ O) and (CH 3 ) 2 CHC( ⁇ O).
  • alkoxycarbonyl include CH 3 OC( ⁇ O), CH 3 CH 2 OC( ⁇ O), CH 3 CH 2 CH 2 OC( ⁇ O), (CH 3 ) 2 CHOC( ⁇ O) and the different pentoxy- or hexoxycarbonyl isomers.
  • alkylcarbonyloxy denotes a straight-chain or branched alkyl bonded to a C( ⁇ O)O moiety.
  • alkylcarbonyloxy examples include CH 3 CH 2 C( ⁇ O)O and (CH 3 ) 2 CHC( ⁇ O)O.
  • (Alkylthio)carbonyl denotes a straight-chain or branched alkylthio group bonded to a C( ⁇ O) moiety.
  • Examples of “(alkylthio)carbonyl” include CH 3 SC( ⁇ O), CH 3 CH 2 CH 2 SC( ⁇ O) and (CH 3 ) 2 CHSC( ⁇ O).
  • Alkoxy(thiocarbonyl) denotes a straight-chain or branched alkoxy group bonded to a C( ⁇ S) moiety.
  • alkoxy(thiocarbonyl) examples include CH 3 OC( ⁇ S), CH 3 CH 2 CH 2 OC( ⁇ S) and (CH 3 ) 2 CHOC( ⁇ S).
  • alkylcarbonylamino denotes alkyl bonded to a C( ⁇ O)NH moiety. Examples of “alkylcarbonylamino” include CH 3 C( ⁇ O)NH and CH 3 CH 2 C( ⁇ O)NH.
  • Trialkylsilyl includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.
  • halogen either alone or in compound words such as “halomethyl”, “haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” include F 3 C, ClCH 2 , CF 3 CH 2 and CF 3 CCl 2 .
  • haloalkenyl examples include Cl 2 C ⁇ CHCH 2 and CF 3 CH 2 ⁇ CH.
  • haloalkoxy examples include CF 3 O, CCl 3 CH 2 O, F 2 CHCH 2 CH 2 O and CF 3 CH 2 O.
  • haloalkylthio examples include CCl 3 S, CF 3 S, CCl 3 CH 2 S and ClCH 2 CH 2 CH 2 S.
  • haloalkylsulfinyl examples include CF 3 S( ⁇ O), CCl 3 S( ⁇ O), CF 3 CH 2 S( ⁇ O) and CF 3 CF 2 S( ⁇ O).
  • haloalkylsulfonyl examples include CF 3 S( ⁇ O) 2 , CCl 3 S( ⁇ O) 2 , CF 3 CH 2 S( ⁇ O) 2 and CF 3 CF 2 S( ⁇ O) 2 .
  • halocycloalkyl examples include chlorocyclopropyl, fluorocyclobutyl and chlorocyclohexyl.
  • C i -C j The total number of carbon atoms in a substituent group is indicated by the “C i -C j ” prefix where i and j are numbers from 1 to 12.
  • C 1 -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2
  • C 4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • unsubstituted in connection with a group such as a ring means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1.
  • optionally substituted means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, the number of optional substituents (when present) range from 1 to 3.
  • the term “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted” or with the term “(un)substituted.”
  • the number of optional substituents may be restricted by an expressed limitation.
  • the phrase “optionally substituted with up to 3 substituents independently selected from R 3a on carbon atom ring members” means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows).
  • the phrase “optionally substituted with up to 5 substituents independently selected from R 3a ” means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows.
  • a “ring” or “ring system” as a component of Formula 1 is carbocyclic (e.g., phenyl or naphthalenyl) or heterocyclic (e.g., pyridinyl).
  • ring member refers to an atom (e.g., C, O, N or S) forming the backbone of a ring.
  • ring system denotes two or more fused rings (e.g., quinazolinyl).
  • nonaromatic includes rings that are fully saturated as well as partially or fully unsaturated, provided that none of the rings are aromatic.
  • aromatic indicates that each of the ring atoms of a fully unsaturated ring are essentially in the same plane and have a p-orbital perpendicular to the ring plane, and that (4n+2) ⁇ electrons, where n is a positive integer, are associated with the ring to comply with Hickel's rule.
  • carbocyclic ring or “carbocycle” denote a ring wherein the atoms forming the ring backbone are selected only from carbon. When a fully unsaturated carbocyclic ring satisfies Hickel's rule, then said ring is also called an “aromatic carbocyclic ring”.
  • saturated carbocyclic ring refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
  • heterocyclic ring denotes a ring or ring system in which at least one atom forming the ring backbone is not carbon (e.g., N, O or S).
  • a heterocyclic ring contains no more than 3 N atoms, no more than 2 O atoms and no more than 2 S atoms.
  • a heterocyclic ring can be a saturated, partially unsaturated or fully unsaturated ring. When a fully unsaturated heterocyclic ring satisfies Hickel's rule, then said ring is also called a “heteroaromatic ring” or “aromatic heterocyclic ring”.
  • heterocyclic rings can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • Q 1 and Q 2 comprises a phenyl or 6-membered heterocyclic ring (e.g., pyridinyl)
  • the ortho, meta and para positions of each ring are relative to the connection of the ring to the remainder of Formula 1.
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
  • salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms.
  • the salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • Formula 1 includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents.
  • Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
  • Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
  • polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
  • polymorphs can have the same chemical composition, they can also differ in composition due to the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
  • a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1.
  • Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
  • Embodiments of the present invention as described in the Summary of the Invention include those described below.
  • Formula 1 includes stereoisomers, N-oxides and salts thereof, and reference to “a compound of Formula 1” includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.
  • each R 3a is independently amino, cyano, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 2 -C 4 alkenyl, C 3 -C 4 cycloalkyl, C 4 -C 6 cycloalkylalkyl, C 4 -C 6 alkylcycloalkyl, C 1 -C 3 alkylthio, C 1 -C 3 alkylsulfinyl, C 1 -C 3 alkylsulfonyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy, C 3 -C 6 cycloalkoxy, C 1 -C 3 alkylsulfonyloxy, C 2 -C 4 alkylcarbonyloxy, C 2 -C 4 alkylcarbonyl, C 1 -C 3 alkylamino, C 2 -C 4 dial
  • each R 3a is independently cyano, halogen, methyl, halomethyl, cyclopropyl, methylthio, methoxy, methylsulfonyloxy, methylcarbonyloxy, methylcarbonyl or —U—V-T.
  • each R 3a is independently cyano, halogen, methyl, halomethyl or methoxy.
  • each R 3a is independently cyano, halogen or methoxy.
  • each R 3a is independently cyano, Br, Cl, F or methoxy.
  • each R 3a is independently Br, Cl or F.
  • each R 3b is independently C 2 -C 4 haloalkenyl, C 5 -C 8 cycloalkylalkenyl, C 5 -C 8 cycloalkylalkynyl, C 4 -C 6 alkoxy, C 4 -C 6 haloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 3 -C 6 haloalkynyloxy, C 4 -C 8 cycloalkylalkoxy, C 4 -C 6 alkylsulfonyloxy, C 4 -C 6 haloalkylsulfonyloxy, C 3 -C 9 trialkylsilyl, C 4 -C 9 trialkylsilylalkyl, C 4 -C 9 trialkylsilylalkoxy, —C( ⁇
  • each R 3b is independently C 5 -C 8 cycloalkylalkenyl, C 5 -C 8 cycloalkylalkynyl, C 4 -C 6 alkoxy, C 4 -C 6 haloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 3 -C 6 haloalkynyloxy, C 4 -C 8 cycloalkylalkoxy, C 4 -C 6 alkylsulfonyloxy, C 4 -C 6 haloalkylsulfonyloxy, C 4 -C 9 trialkylsilylalkoxy, —C( ⁇ S)NR 9a R 9b , —CR 10a ⁇ NOR 10b , —ON ⁇ CR 11a R 11b or -A(CR 12a R 12b ) n W.
  • each R 3b is independently C 5 -C 8 cycloalkylalkynyl, C 4 -C 6 alkoxy, C 4 -C 6 haloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 3 -C 6 haloalkynyloxy, C 4 -C 8 cycloalkylalkoxy, C 4 -C 9 trialkylsilylalkoxy, —C( ⁇ S)NR 9a R 9b , —CR 10a ⁇ NOR 10b , —ON ⁇ CR 11a R 11b or -A(CR 12a R 12b ) n W.
  • each R 3b is independently C 5 -C 8 cycloalkylalkynyl, C 4 -C 6 alkoxy, C 4 -C 6 haloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 4 -C 8 cycloalkylalkoxy, C 4 -C 9 trialkylsilylalkoxy, —C( ⁇ S)NR 9a R 9b , —CR 10a ⁇ NOR 10b , —ON ⁇ CR 11a R 11b or -A(CR 12a R 12b ) n W.
  • each R 3b is independently C 5 -C 8 cycloalkylalkynyl, C 4 -C 6 alkoxy, C 4 -C 6 haloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 4 -C 8 cycloalkylalkoxy, C 4 -C 9 trialkylsilylalkoxy, —CR 10a ⁇ NOR 9 , —ON ⁇ CR 11a R 11b or -A(CR 12a R 12b ) n W.
  • each R 3b is independently C 5 -C 8 cycloalkylalkynyl, C 4 -C 6 alkoxy, C 4 -C 6 haloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy, C 4 -C 8 cycloalkylalkoxy, —CR 10a ⁇ NOR 9 or -A(CR 12a R 12b ) n W.
  • each R 3b is independently C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 3 -C 6 alkynyloxy or -A(CR 12a R 12b ) n W.
  • each R 3b is -A(CR 12a R 12b ) n W.
  • each W is independently a 3- to 7-membered heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O, up to 2 S and up to 2 N atoms, wherein up to 1 carbon atom ring member is C( ⁇ O), the ring optionally substituted with up to 3 substituents independently selected from R 13 on carbon atom ring members and R 14 on nitrogen atom ring members.
  • each W is independently a 3- to 6-membered heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O, up to 2 S and up to 2 N atoms, the ring optionally substituted with up to 3 substituents independently selected from R 13 on carbon atom ring members and R 14 on nitrogen atom ring members.
  • each W is independently a 3- to 5-membered heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O and up to 2 N atoms, the ring optionally substituted with up to 2 substituents independently selected from R 13 on carbon atom ring members and R 14 on nitrogen atom ring members.
  • each W is independently a 3- to 5-membered heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O and up to 2 N atoms, the ring optionally substituted with up to 2 substituents independently selected from R 13 on carbon atom ring members.
  • each W is independently a 5-membered heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O and up to 2 N atoms, the ring optionally substituted with up to 2 substituents independently selected from R 13 on carbon atom ring members.
  • each W is independently a 3- to 5-membered heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O and up to 2 N atoms.
  • R 5b is H, —CH( ⁇ O), C 1 -C 3 alkyl, C 1 -C 2 haloalkyl, C 2 -C 4 cyanoalkyl, C 2 -C 3 alkoxyalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 alkoxycarbonyl, C 2 -C 4 (alkylthio)carbonyl or C 2 -C 4 alkoxy(thiocarbonyl).
  • each R 10a is independently H, methyl or halomethyl.
  • each R 10b and R 10c is independently H, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 3 -C 4 cycloalkyl or C 3 -C 4 halocycloalkyl.
  • each R 10b and R 10c is independently H, methyl, halomethyl or cyclopropyl.
  • each R 11a and R 11b is independently H, methyl or halomethyl.
  • each R 12a is independently H, cyano, halogen or methyl.
  • each R 12a is independently H or methyl.
  • each R 12b is independently H or methyl.
  • each R 13 is independently cyano, halogen, methyl, halomethyl, methoxy or halomethoxy.
  • each R 13 is independently halogen, methyl, halomethyl or methoxy.
  • each R 18 and R 21 is independently cyano, C 3 -C 6 cycloalkyl or C 1 -C 3 alkoxy.
  • each R 18 and R 21 is independently cyano, cyclopropyl or methoxy.
  • each R 23a and R 23b is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl.
  • each R 23a and R 23b is independently H, methyl or halomethyl.
  • each R 24 is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl.
  • Embodiments of this invention can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds useful for preparing the compounds of Formula 1 unless further defined in the Embodiments.
  • embodiments of this invention including Embodiments 1-143 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention. Combinations of Embodiments 1-143 are illustrated by:
  • Specific embodiments include compounds of Formula 1 selected from the group consisting of:
  • Compounds of Formula 1 can be prepared as shown in Scheme 1.
  • a compound of Formula 2 is first treated with an organometallic agent of Formula 3 such as an alkyl lithium base (e.g., n-butyllithium, s-butyllithium or lithium diisopropylamide) or a Grignard reagent in a solvent such as toluene, diethyl ether, tetrahydrofuran or dimethoxymethane at temperatures ranging from about ⁇ 78° C. to ambient temperature.
  • Anions of Formula 2a are then contacted with an electrophile of Formula 4, 5 or 6.
  • an appropriate electrophile will depend on the desired compound of Formula 1 and will be apparent to one skilled in chemical synthesis.
  • chlorosulfides of formula Q 2 SCl or disulfies formula of Q 2 S—S-Q 2 provide compounds of Formula 1a (i.e. Formula 1 wherein X is S)
  • aldehydes of the formula Q 2 CHO i.e. Formula 5
  • compounds of Formula 1b i.e. Formula 1 wherein X is CH(OH)
  • nitrosobenzenes of formula Q 2 -N ⁇ O i.e. Formula 6
  • compounds of Formula 1c i.e. Formula 1 wherein X is N(OH)
  • Electrophiles of Formulae 4, 5 and 6 are commercially available and can be prepared by methods known in the art.
  • Compounds of Formula 2 are known and can be prepared by the method disclosed in Scheme 6 below, and by a variety of methods disclosed in the chemical literature.
  • compounds of Formula 1b can be prepared from the corresponding ketone compounds of Formula 7 using standard reduction techniques.
  • Typical reaction conditions involve contacting a compound of Formula 7 with a boron-based reducing agent such as sodium borohydride or sodium triacetoxyborohydride in a solvent such as methanol, ethanol or tetrahydrofuran.
  • a boron-based reducing agent such as sodium borohydride or sodium triacetoxyborohydride
  • solvent such as methanol, ethanol or tetrahydrofuran.
  • Other techniques known to those skilled in the art may also be employed.
  • For relevant references see, for example, Journal of the American Chemical Society 2006, 128, 9998-9999 and PCT Publication WO 2010/030922 A1 (Examples 8 and 11).
  • compounds of Formula 7 can also be treated with alkylmagnesium halides to provide compounds of Formula 1d (i.e. Formula 1 wherein X is C(OH)R 5a and R 5a is C 1 -C 6 alkyl).
  • the reaction is run in presence of zinc chloride and in a solvent such as diethyl ether or tetrahydrofuran at temperatures from about 0-100° C.
  • a solvent such as diethyl ether or tetrahydrofuran
  • intermediates of Formula 7 can be prepared using a method analogous to Scheme 1, wherein anions of Formula 2a are treated with benzoyl chlorides of formula Q 1 C( ⁇ O)Cl (i.e. Formula 8) or benzamides of formula Q 1 C( ⁇ O)N(Me)OMe (i.e. Formula 9) to provide compounds of Formula 7.
  • the electrophile is Q 1 C( ⁇ O)Cl
  • the addition of a second organometallic reagent such as zinc chloride, zinc bromide or a monovalent copper salt such as copper(I) iodide or copper(I) cyanide before the addition of the electrophile promotes reactivity.
  • a second organometallic reagent such as zinc chloride, zinc bromide or a monovalent copper salt such as copper(I) iodide or copper(I) cyanide
  • intermediates of Formula 7 can also be prepared from compounds of Formula 10 using Friedel-Crafts acylation conditions as illustrated in Scheme 5.
  • a compound of Formula 10 is contacted with an acid chloride of Formula 11 in the presence of a Lewis acid (e.g., aluminum chloride, boron trifluoride diethyl etherate or tin tetrachloride) in a solvent such as dichloromethane, tetrachloroethane or nitrobenzene, at temperatures ranging between about 0 to 200° C.
  • a Lewis acid e.g., aluminum chloride, boron trifluoride diethyl etherate or tin tetrachloride
  • a solvent such as dichloromethane, tetrachloroethane or nitrobenzene
  • intermediates of Formula 2 are readily prepared from compounds of Formula 10 by treatment with a halogenating agent.
  • Suitable halogenating agents for this method include N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), bromine, sodium bromite, thionyl chloride, oxalyl chloride, phenylphosphonic dichloride or phosgene. Particularly useful is N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS).
  • Suitable solvents for this reaction include, for example, N,N-dimethylformamide, N,N-dimethylacetamide, dichloromethane, chloroform, chlorobutane, benzene, xylenes, chlorobenzene, tetrahydrofuran, p-dioxane, acetonitrile, and the like.
  • a base such as sodium carbonate, triethylamine, pyridine, N,N-dimethylaniline, and the like can be added.
  • Typical reaction temperatures range from about ambient temperature to 200° C.
  • intermediates of Formula 10 can be prepared by reaction of a 5-bromo or 5-iodo pyrazole of Formula 12 under transition-metal-catalyzed cross-coupling reaction conditions.
  • reaction of a pyrazole of Formula 12 is contacted with a compound of formula Q 1 -M 2 (i.e. Formula 13) in the presence of a suitable palladium, copper or nickel catalyst, to provide a compound of Formula 10.
  • Suitable compounds of formula Q 1 -M 2 include organoboronic acids (e.g., M 2 is B(OH) 2 ), organoboronic esters (e.g., M 2 is B(—OC(CH 3 ) 2 C(CH 3 ) 2 O—)), organotrifluoroborates (e.g., M 2 is BF 3 K), organotin reagents (e.g., M 2 is Sn(n-Bu) 3 , Sn(Me) 3 ), Grignard reagents (e.g., M 2 is MgBr or MgCl) or organozinc reagents (e.g., M 2 is ZnBr or ZnCl).
  • organoboronic acids e.g., M 2 is B(OH) 2
  • organoboronic esters e.g., M 2 is B(—OC(CH 3 ) 2 C(CH 3 ) 2 O—
  • organotrifluoroborates e.g.,
  • Suitable metal catalysts include, but are not limited to: palladium(II) acetate, palladium(II) chloride, tetrakis(triphenylphosphine)-palladium(0), bis(triphenylphosphine)palladium(II) dichloride, dichloro[1,1′-bis(diphenyl-phosphino)ferrocene]palladium(II), bis(triphenylphosphine)dichloronickel(II) and copper(I) salts (e.g., copper(I) iodide, copper(I) bromide, copper(I) chloride, copper(I) cyanide or copper(I) triflate).
  • palladium(II) acetate palladium(II) chloride
  • tetrakis(triphenylphosphine)-palladium(0) bis(triphenylphosphine)palladium(II) dichloride, dichloro[
  • Optimal conditions for each reaction will depend on the catalyst used and the counterion attached to the coupling reagent (i.e. M 2 ), as is understood by one skilled in the art.
  • a ligand such as a substituted phosphine or a substituted bisphosphinoalkane promotes reactivity.
  • a base such as an alkali carbonate, tertiary amine or alkali fluoride may be necessary for some reactions involving organoboron reagents of the formula Q 1 -M 2 .
  • intermediates of Formula 10 can be prepared by cyclization of enones of Formula 14 with an appropriately substituted hydrazine of formula NH 2 NH—CHR 1 R 1a (i.e. Formula 15) and subsequent oxidation of pyrazolines of Formula 16.
  • Useful oxidizing reagents include bromine (for conditions see, for example, Indian Journal of Heterocyclic Chemistry, 2001, 11(1), 21-26), elemental sulfur, manganese dioxide, 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), chloranil (for conditions see, for example, Russian Journal of Organic Chemistry 2006, 42(8), 1113-1119) and oxygen optionally in the presence of a metal catalyst such as cobalt acetate (for conditions see, for example, Tetrahedron 2006, 62(11), 2492-2496 and Chinese Chemical Letters 2008, 19(9), 1013-1016).
  • Useful solvents for this reaction include N,N-dimethylformamide, tetrahydrofuran, toluene, water, dichloromethane, tetrachloroethane, and mixtures of these or similar solvents, at temperatures from ambient to 200° C.
  • the reaction of hydrazines with enones and the preparation of the enones is well-known in the art, see, for example, Synthesis 2012, 44, 2401-2407 and PCT Publication WO 2010/030922 A1 (Example 4, Step B). Also, in the present disclosure, Example 1, Step C illustrates the method of Scheme 8.
  • compounds of Formula 12 can be prepared by alkylation of corresponding pyrazoles of Formula 17 with an alkylating agent of formula CHR 1 R 1a -L 2 (i.e. Formula 18) wherein L 2 is a leaving group such as halogen or (halo)alkylsulfonate (e.g., Cl, Br, I, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate).
  • halogen or (halo)alkylsulfonate e.g., Cl, Br, I, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate.
  • Particularly useful alkylating agents for preparing compounds of Formula 12 are H are diazomethane or iodomethane using general procedures known in the art, such as those described in Tetrahedron Letters 2009, 50(49), 6783-6786 and PCT Publication WO 2010/030922 A1 (Example 9, Step B).
  • Compounds of Formula 1 wherein X is O, S or NR 4 can be prepared by reacting compounds of Formula 19 (e.g., 4-hydroxypyrazoles for X being O, 4-mercaptopyrazoles for X being S and 4-aminopyrazoles for X being NR 4 ) with compounds of Formula 20 where L 2 is a leaving group such as halogen or (halo)alkylsulfonate (e.g., Cl, Br, I, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate), optionally in the presence of a metal catalyst, and generally in the presence of a base and a polar aprotic solvent such as N,N-dimethylformamide or dimethyl sulfoxide.
  • compounds of Formula 19 e.g., 4-hydroxypyrazoles for X being O, 4-mercaptopyrazoles for X being S and 4-aminopyrazoles for X being NR 4
  • L 2 is Br or I or a sulfonate such as —OS(O) 2 CF 3 or —OS(O) 2 (CF 2 ) 3 CF 3 .
  • a metal catalyst such as copper salt complexes (e.g., CuI with N,N′-dimethylethylenediamine, proline or bipyridyl), or palladium complexes (e.g., tris(dibenzylideneacetone)dipalladium(0)) or palladium salts (e.g., palladium acetate) with ligands such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl or 2,2′-bis-(diphenylphosphino)1,1′-binaphthalene, and with a base
  • copper salt complexes e.g., CuI
  • compounds of Formula 1 can also be prepared by reaction of a 5-bromo or 5-iodo pyrazole of Formula 21 with an organometallic compound of Formula 22 under transition-metal-catalyzed cross-coupling reaction conditions analogous to those described for Scheme 7.
  • a pyrazole of Formula 21 Reaction of a pyrazole of Formula 21 with a boronic acid, trialkyltin or an organomagnesium reagent of Formula 22 in the presence of a palladium or nickel catalyst and optionally a ligand (e.g., triphenylphosphine, dibenzylideneacetone, dicyclohexyl(2′,6′-dimethoxy[1,1′-biphenyl]-2-yl)phosphine) and a base affords a compound of Formula 1.
  • a ligand e.g., triphenylphosphine, dibenzylideneacetone, dicyclohexyl(2′,6′-dimethoxy[1,1′-biphenyl]-2-yl
  • a compound of Formula 22 wherein M 3 is B(OH) 2 , B OC(CH 3 ) 2 C(CH 3 ) 2 O ) or B(O-i-Pr) 3 Li reacts with a 5-bromo- or 5-iodopyrazole of Formula 21 in the presence of dichlorobis(triphenylphosphine) palladium(II) and an aqueous base such as sodium carbonate or potassium hydroxide, in solvents such as 1,4-dioxane, 1,2-dimethoxyethane, toluene or ethyl alcohol, or under anhydrous conditions with the use of a ligand such as phosphine oxide or phosphite ligand (e.g., diphenylphosphine oxide) and potassium fluoride in a solvent such as 1,4-dioxane to provide a compound of Formula 1.
  • a ligand such as phosphine oxide or phosphite ligand
  • Compounds of Formula 1 can be subjected to various nucleophilic, metalation and oxidation reactions to add substituents or modify existing substituents, and thus provide other functionalized compounds of Formula 1.
  • compounds of Formula 1e i.e. Formula 1 wherein X in NR 4 and R 4 is other than H
  • compounds of Formula 1f i.e. Formula 1 wherein X is NH
  • an electrophile comprising R 4 (i.e. Formula 23) typically in the presence of a base such as sodium hydride and a polar solvent such as N,N-dimethylformamide.
  • electrophile comprising R 4 means a chemical compound capable of transferring an R 4 moiety to a nucleophile (such as the nitrogen atom in Formula 1f).
  • electrophiles comprising R 4 have the formula R 4 L 3 wherein L 3 is a nucleofuge (i.e. leaving group in nucleophilic reactions).
  • Typical nucleofuges include halogens (e.g., Cl, Br, I) and sulfonates (e.g., OS(O) 2 CH 3 , OS(O) 2 CF 3 , OS(O) 2 -(4-CH 3 -Ph)).
  • electrophiles comprising R 4 do not comprise a nucleofuge; an example is sulfur trioxide (SO 3 ) which, after deprotonation (such as by a base of the formula M + H ⁇ wherein M + is a cation) of the nitrogen atom in Formula 1f, can bond to the nitrogen atom as a —S( ⁇ O) 2 OM substituent.
  • SO 3 sulfur trioxide
  • a fluoro can be introduced at the 3-position of the pyrazole ring by treating compounds Formula 1h (i.e. Formula 1 wherein R 2 is chlorine) with potassium fluoride or cesium fluoride in presence of a solvent such as dimethyl sulfoxide or N,N-dimethylformamide at about 0-25° C. for about 30 minutes to 4 h, using procedures such as those described in Zhurnal Organicheskoi Khimii 1983, 19, 2164-2173.
  • Formula 1h i.e. Formula 1 wherein R 2 is chlorine
  • a solvent such as dimethyl sulfoxide or N,N-dimethylformamide
  • sulfoxides and sulfones of Formula 1i can be prepared by oxidation of compounds of Formula 1a (i.e. Formula 1 wherein X is S).
  • an oxidizing agent in an amount of about 1 to 4 equivalents, depending on the oxidation state of the desired product, is added to a mixture of a compound of Formula 1a and a solvent.
  • Useful oxidizing agents include Oxone® (potassium peroxymonosulfate), potassium permanganate, hydrogen peroxide, sodium periodate, peracetic acid and 3-chloroperbenzoic acid.
  • the solvent is selected with regard to the oxidizing agent employed.
  • Aqueous ethanol or aqueous acetone is preferably used with potassium peroxymonosulfate, and dichloromethane is generally preferable with 3-chloroperbenzoic acid.
  • Useful reaction temperatures typically range from about ⁇ 78 to 90° C. Oxidation reactions of this type are described in J. Agric. Food Chem. 1984, 32, 221-226 and J. Agric. Food Chem. 2008, 56, 10160-10167.
  • R 3a and/or R 3b substituents attached to Q 1 and Q 2 may be more conveniently incorporated after forming the central pyrazole ring with Q 1 and Q 2 already attached.
  • compounds of Formula 1j i.e.
  • Formula 1 wherein Q 1 is phenyl and R 3b is alkoxy, alkenyloxy, alkynyloxy, cycloalkoxy, and the like) can be prepared by reacting hydroxyphenyl derivatives of Formula 24 with compounds of formula 25 wherein L 2 is a suitable leaving group such as halogen or (halo)alkylsulfonate (e.g., Cl, Br, I, p-toluenesulfonate, methanesulfonate or trifluoromethanesulfonate), in the presence of a base such as potassium carbonate, potassium tert-butoxide, sodium hydride or triethylamine, and in an aprotic solvent such as N,N-dimethylformamide, acetonitrile, dimethylsulfoxide or tetrahydrofuran at a temperature between about ⁇ 20 and 150° C.
  • a base such as potassium carbonate, potassium tert-butoxide, sodium hydride
  • hydroxyphenyl derivatives of Formula 24 can be prepared from boronic acids or esters of Formula 26 via oxidative hydroxylation.
  • oxidizing agents include hydrogen peroxide and N-oxides such as N,N,4-trimethylbenzenamine N-oxide according to procedures reported in Tetrahedron Letters 2012, 53, 6004-6007 and Organic Letters 2012, 14(13), 3494-3497.
  • the intermediate boronic acids or esters of Formula 26 can be prepared by contacting compounds of Formula 27 wherein L 3 is Cl, Br, I or a triflate group with a boronic acid or ester of Formula 28.
  • the reaction is carried out in the presence a palladium catalyst such as PdCl 2 dppf (PdCl 2 -1,1′-bis(diphenylphosphino)ferrocene) and a base such as potassium acetate in a solvent such as dioxane at about 80 to 100° C.
  • a palladium catalyst such as PdCl 2 dppf (PdCl 2 -1,1′-bis(diphenylphosphino)ferrocene)
  • a base such as potassium acetate
  • the stoichiometry of this method requires at least one molar equivalent of the boronic acid or ester to obtain complete conversion of the compound of Formula 27 to the corresponding compound of Formula 26.
  • boronic acid typically used, often at least 1.5 to 2.0 molar equivalents relative to the compound of Formula 27.
  • boronic acids, esters, and their derivatives can be used in the method of Scheme 17.
  • Particularly useful derivatives include, for example, trialkoxy boranes such as trimethoxyborane.
  • Coupling reactions with boronic acids or derivatives in the presence of palladium catalysts are known, and the wide variety of known general procedures can be readily adapted by one skilled in the art for use in the method of Scheme 17. For articles about this type of functional group transformation, see, for example, Tetrahedron 2000, 56, 9655-9662 and Chemical Communications 2004, 1, 38.
  • Schemes 15-18 can alternatively be carried out at other stages in the preparation of pyrazoles of Formula 1.
  • compounds of Formula 31 can be prepared (present Example 2, Step C and Example 3, Step A illustrate the preparation of a compound of Formula 31 using the method Scheme 15), and then subsequently reduced using the method described in Scheme 2 or alkylated using the method described in Scheme 3 to provide compounds of Formula 1j wherein X is CH(OH) or C(OH)R 5a and R 5a is other then H, respectively.
  • R 3b group attached to Q 1 or Q 2 Numerous other methods known to those skilled in the art can be employed for the construction of an R 3b group attached to Q 1 or Q 2 .
  • compounds of Formula 1k i.e. Formula 1 wherein Q 1 is phenyl, R 3b is W and W is a heterocycle linked through nitrogen
  • compounds of Formula 32 wherein L 3 is Cl, Br, I or a triflate group with heterocycles of Formula 33 using Buchwald-Hartwig coupling reaction conditions.
  • these reactions are conducted in an inert solvent in the presence of a suitable ligand, a copper (I) salt (e.g., CuI or CuBr) and a base (e.g., sodium or potassium carbonate) at about ambient temperature to 230° C. for about 1 to 48 h.
  • a suitable ligand e.g., a copper (I) salt (e.g., CuI or CuBr) and a base (e.g., sodium or potassium carbonate)
  • Typical ligands include 1,2-diaminocyclohexane and phenanthroline.
  • Suitable solvents include dioxane, 1,2-diethoxyethane and toluene. Conditions for Buchwald-Hartwig couplings are well documented in the literature, see for example, Tetrahedron Letters, 2010, 52(38), 5052 and Journal of Medicinal Chemistry 2010, 53(10), 31-8.
  • compounds of Formula 1k i.e. Formula 1 wherein Q 1 is phenyl, R 3b is W and W is a heterocycle linked through nitrogen
  • compounds of Formula 1k can be prepared from boronic acids or esters of Formula 26 and compounds of Formula 33 using Chan-Lam coupling conditions.
  • the reaction is run in presence of a Cu(II) salt, oxygen, and a base at about ambient temperature to 150° C. for about 24 to 72 h.
  • Suitable Cu(II) salts include are Cu(OAc) 2 , CuBr 2 and CuI 2 , suitable bases include pyridine, quinoline and triethylamine, and suitable solvents include dichloromethane, chloroform, diethyl ether and tetrahydrofuran. For representative conditions see Tetrahedron Letters, 1998, 38, 2941 and PCT Patent Publication WO 2003/072547.
  • Cyclic boronates of Formula 30 are also useful in the method of Scheme 21.
  • R 3b groups include well documented functional group transformations of ketones, esters, acids, aldehydes, nitriles and the like.
  • reaction of an aldehyde or ketone of Formula 35 with a hydrazine of Formula 36 provides compounds of Formula 1n (i.e. Formula 1 wherein Q 1 is phenyl and R 3a is —CR 10c ⁇ NNR 9a R 9b ).
  • R 3a is —CR 10c ⁇ NNR 9a R 9b
  • Tetrahedron 2000, 56(41), 8071-8076 Journal of Organic Chemistry 2005, 70(2), 596-602 and Synthetic Communications 1997, 27(7), 1199-1207.
  • Aldehydes and ketones of Formula 35 can be prepared from the corresponding bromo, iodo or triflate derivatives via transition metal-catalyzed cross-coupling reactions.
  • transition metal-catalyzed cross-coupling reactions See J. Am. Chem. Soc., 2008, 130, 15549-15563 , Journal of Medicinal Chemistry 2003, 46, 5651-5662 and Tetrahedron 2003, 59, 8199-8202.
  • aromatic amines anilines
  • aromatic halides such as bromides or iodides
  • alcohols under copper-catalyzed conditions such as the Ullmann reaction or known modifications thereof, to provide compounds of Formula 1 that contain alkoxy substituents.
  • some halogen groups such as fluorine or chlorine, can be displaced with alcohols under basic conditions to provide compounds of Formula 1 containing the corresponding alkoxy substituents.
  • Step B Preparation of (2Z)-1-(4-bromo-2,6-difluorophenyl)-3-hydroxy-2-buten-1-one
  • Step D Preparation of [5-(4-bromo-2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-4-yl](2-chloro-4-fluorophenyl)methanone
  • Step E Preparation of (2-chloro-4-fluorophenyl)[5-[2,6-difluoro-4-(1H-pyrazol-1-yl)phenyl]-1,3-dimethyl-1H-pyrazol-4-yl]methanone
  • reaction mixture was sparged with argon gas for 20 minutes and then trans-N,N-dimethyl-1,2-cyclohexanediamine (0.02 mL, 0.14 mmol) was added and the mixture was heated at 110° C. for 24 h. After cooling to room temperature, the reaction mixture was filtered through a pad of Celite® (diatomaceous filter aid) on a sintered glass frit funnel. The filtrate was added to water (50 mL) and then extracted with ethyl acetate (2 ⁇ 50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel eluting with 20% ethyl acetate in petroleum ether to provide the title compound as an off-white solid (280 mg).
  • Step F Preparation of ⁇ -(2-chloro-4-fluorophenyl)-5-[2,6-difluoro-4-(1H-pyrazol-1-yl)phenyl]-1,3-dimethyl-1H-pyrazole-4-methanol
  • Step A Preparation of (2-chloro-4-fluorophenyl)[5-[2,6-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-dimethyl-1H-pyrazol-4-yl]methanone
  • Step B Preparation of (2-chloro-4-fluorophenyl)[5-(2,6-difluoro-4-hydroxyphenyl)-1,3-dimethyl-1H-pyrazol-4-yl]methanone
  • Step C Preparation of (2-chloro-4-fluorophenyl)[5-[4-(cyclopropylmethoxy)-2,6-difluorophenyl]-1,3-dimethyl-1H-pyrazol-4-yl]methanone
  • Step D Preparation of ⁇ -(2-chloro-4-fluorophenyl)-5-[4-(cyclopropylmethoxy)-2,6-difluorophenyl]-1,3-dimethyl-1H-pyrazole-4-methanol
  • Step A Preparation of (2-chloro-4-fluorophenyl)[5-[2,6-difluoro-4-(3-methylbutoxy)phenyl]-1,3-dimethyl-1H-pyrazol-4-yl]methanone
  • Step B Preparation of ⁇ -(2-chloro-4-fluorophenyl)-5-[2,6-difluoro-4-(3-methylbutoxy)phenyl]-1,3-dimethyl-1H-pyrazole-4-methanol
  • the present disclosure also includes Tables 1A through 215A, each of which is constructed the same as Table 1 above, except that the row heading in Table 1 (i.e. “Q 2 is 2,4,6-tri-F-Ph, (R 3a ) p is 2,6-di-F”) is replaced with the respective row headings shown below.
  • Table 1A the row heading is “Q 2 is 2,4,6-tri-F-Ph, (R 3a ) p is 2-F”, and R 3b is as defined in Table 1 above.
  • Table 1A specifically discloses 5-[2-fluoro-4-(-propyn-1-yloxy)phenyl]-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-4-amine.
  • Tables 2A through 215A are constructed similarly.
  • Table Row Heading 1A Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-F.
  • 2A Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Cl.
  • 3A Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Br.
  • 4A Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Me.
  • 5A Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 6A Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 13A Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 14A Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 15A Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 16A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2,6-di-F.
  • 17A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-F.
  • 18A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Cl.
  • 19A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Br.
  • 20A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Me.
  • 21A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 22A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 23A Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2,6-di-Cl.
  • 24A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 25A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-F.
  • 26A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 27A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Br.
  • 28A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Me.
  • 29A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl
  • 30A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 31A Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2,6-di-Cl.
  • 32A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2,6-di-F.
  • 33A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-F.
  • 34A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Cl.
  • 35A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Br.
  • 36A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Me.
  • 37A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 38A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 39A Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2,6-di-Cl.
  • 40A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2,6-di-F.
  • 41A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-F.
  • 42A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Cl.
  • 43A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Br. 44A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Me. 45A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-F, 6-Cl. 46A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Cl, 6-F. 47A Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 53A Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 54A Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 55A Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2,6-di-Cl.
  • 56A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2,6-di-F.
  • 57A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-F.
  • 58A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Cl.
  • 59A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Br.
  • 60A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Me
  • 61A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 62A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 63A Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2,6-di-Cl 64A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2,6-di-F.
  • 65A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-F.
  • 66A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Cl.
  • 67A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Br.
  • 68A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Me.
  • 69A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 70A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 71A Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 77A Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 78A Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 79A Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2,6-di-Cl.
  • 80A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 81A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-F.
  • 82A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Cl.
  • 83A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Br.
  • 84A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Me.
  • 85A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 86A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 87A Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 88A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 89A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-F.
  • 90A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl.
  • 91A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Br.
  • 92A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Me.
  • 93A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 94A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 95A Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 96A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 97A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-F.
  • 98A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Cl.
  • 99A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Br.
  • 100A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Me 101A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 102A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 103A Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 104A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 105A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-F.
  • 106A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl.
  • 107A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Br.
  • 108A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Me.
  • 109A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 110A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 111A Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 112A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 113A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-F.
  • 114A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 115A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Br.
  • 116A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Me.
  • 117A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl 118A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 119A Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2,6-di-Cl.
  • 120A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 121A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-F.
  • 122A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 123A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Br.
  • 124A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Me.
  • 125A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 126A Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 127A Q 2 is 2,6-di-Br-4-Me—Ph
  • (R 3a ) p is 2,6-di-Cl.
  • 128A Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2,6-di-F.
  • 129A Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2-F.
  • 130A Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Cl.
  • 131A Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Br.
  • 132A Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Me.
  • 133A Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 134A Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 135A Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 136A Q 2 is 2-Cl-4-F, (R 3a ) p is 2,6-di-F.
  • 137A Q 2 is 2-Cl-4-F, (R 3a ) p is 2-F.
  • 138A Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Cl.
  • 139A Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Br.
  • 140A Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Me.
  • 141A Q 2 is 2-Cl-4-F, (R 3a ) p is 2-F, 6-Cl 142A Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Cl, 6-F 143A Q 2 is 2-Cl-4-F, (R 3a ) p is 2,6-di-Cl.
  • 144A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2,6-di-F.
  • 145A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-F.
  • 146A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Cl.
  • 147A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Br.
  • 148A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Me.
  • 149A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-F, 6-Cl.
  • 150A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Cl, 6-F.
  • 151A Q 2 is 2-Cl-4-Me, (R 3a ) p is 2,6-di-Cl.
  • 152A Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2,6-di-F.
  • 153A Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-F
  • 154A Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Cl.
  • 155A Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Br.
  • 162A Q 2 is 2-Br-4-F, (R 3a ) p is 2-Cl.
  • 163A Q 2 is 2-Br-4-F, (R 3a ) p is 2-Br.
  • 164A Q 2 is 2-Br-4-F, (R 3a ) p is 2-Me.
  • 165A Q 2 is 2-Br-4-F, (R 3a ) p is 2-F, 6-Cl.
  • 166A Q 2 is 2-Br-4-F, (R 3a ) p is 2-Cl, 6-F.
  • 167A Q 2 is 2-Br-4-F, (R 3a ) p is 2,6-di-Cl.
  • 168A Q 2 is 2-Br-4-Me, (R 3a ) p is 2,6-di-F.
  • 169A Q 2 is 2-Br-4-Me, (R 3a ) p is 2-F.
  • 170A Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Cl.
  • 171A Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Br.
  • 172A Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Me.
  • 173A Q 2 is 2-Br-4-Me, (R 3a ) p is 2-F, 6-Cl.
  • 174A Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Cl, 6-F. 175A Q 2 is 2-Br-4-Me, (R 3a ) p is 2,6-di-Cl. 176A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2,6-di-F. 177A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-F. 178A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Cl. 179A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Br.
  • 180A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Me.
  • 181A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-F, 6-Cl.
  • 182A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Cl, 6-F.
  • 183A Q 2 is 2-Br-4-MeO, (R 3a ) p is 2,6-di-Cl.
  • 184A Q 2 is 2,4-di-Cl, (R 3a ) p is 2,6-di-F.
  • 185A Q 2 is 2,4-di-Cl, (R 3a ) p is 2-F.
  • 192A Q 2 is 2,6-di-Cl, (R 3a ) p is 2,6-di-F.
  • 193A Q 2 is 2,6-di-Cl, (R 3a ) p is 2-F.
  • 194A Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Cl.
  • 195A Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Br.
  • 196A Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Me.
  • 197A Q 2 is 2,6-di-Cl, (R 3a ) p is 2-F, 6-Cl.
  • 198A Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Cl, 6-F.
  • 199A Q 2 is 2,6-di-Cl, (R 3a ) p is 2,6-di-Cl.
  • 200A Q 2 is 2,4-di-Me, (R 3a ) p is 2,6-di-F.
  • 201A Q 2 is 2,4-di-Me, (R 3a ) p is 2-F.
  • 202A Q 2 is 2,4-di-Me, (R 3a ) p is 2-Cl.
  • 203A Q 2 is 2,4-di-Me, (R 3a ) p is 2-Br.
  • 204A Q 2 is 2,4-di-Me, (R 3a ) p is 2-Me.
  • 205A Q 2 is 2,4-di-Me, (R 3a ) p is 2-F, 6-Cl.
  • 206A Q 2 is 2,4-di-Me, (R 3a ) p is 2-Cl, 6-F.
  • 207A Q 2 is 2,4-di-Me, (R 3a ) p is 2,6-di-Cl.
  • 208A Q 2 is 2,6-di-Me, (R 3a ) p is 2,6-di-F.
  • 209A Q 2 is 2,6-di-Me, (R 3a ) p is 2-F.
  • 210A Q 2 is 2,6-di-Me, (R 3a ) p is 2-Cl 211A Q 2 is 2,6-di-Me, (R 3a ) p is 2-Br.
  • 212A Q 2 is 2,6-di-Me, (R 3a ) p is 2-Me.
  • 213A Q 2 is 2,6-di-Me, (R 3a ) p is 2-F, 6-Cl.
  • 214A Q 2 is 2,6-di-Me, (R 3a ) p is 2-Cl, 6-F.
  • 215A Q 2 is 2,6-di-Me, (R 3a ) p is 2,6-di-Cl.
  • the present disclosure also includes Tables 1B through 215B, each of which is constructed the same as Table 2 above, except that the row heading in Table 2 (i.e. “Q 2 is 2,4,6-tri-F-Ph, (R 3a ) p is 2,6-di-F”) is replaced with the respective row headings shown below.
  • Table 1B the row heading is “Q 2 is 2,4,6-tri-F-Ph, (R 3a ) p is 2-F”, and R 3b is as defined in Table 2 above.
  • Table 1B specifically discloses 5-[2-fluoro-4-(-propyn-1-yloxy)phenyl]-1,3-dimethyl- ⁇ -(2,4,6-trifluorophenyl)-1H-pyrazol-4-methanol.
  • Tables 2B through 215B are constructed similarly.
  • Table Row Heading 1B Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-F.
  • 2B Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Cl.
  • 3B Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Br.
  • 4B Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Me.
  • 5B Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 6B Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 13B Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 14B Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 15B Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 16B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2,6-di-F.
  • 17B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-F.
  • 18B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Cl.
  • 19B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Br.
  • 20B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Me.
  • 21B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 22B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 23B Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2,6-di-Cl.
  • 24B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 25B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-F.
  • 26B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 27B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Br.
  • 28B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Me.
  • 29B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl 30B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 31B Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2,6-di-Cl.
  • 32B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2,6-di-F.
  • 33B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-F.
  • 34B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Cl.
  • 35B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Br.
  • 36B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Me.
  • 37B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 38B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 39B Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2,6-di-Cl.
  • 40B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2,6-di-F.
  • 41B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-F.
  • 42B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Cl.
  • 43B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Br. 44B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Me. 45B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-F, 6-Cl. 46B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Cl, 6-F. 47B Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 48B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2,6-di-F.
  • 49B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-F.
  • 50B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-Cl.
  • 51B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-Br.
  • 52B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-Me.
  • 53B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 54B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 55B Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2,6-di-Cl.
  • 56B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2,6-di-F.
  • 57B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-F.
  • 58B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Cl.
  • 59B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Br.
  • 60B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Me
  • 61B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 62B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 63B Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2,6-di-Cl 64B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2,6-di-F.
  • 65B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-F.
  • 66B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Cl.
  • 67B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Br.
  • 68B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Me.
  • 69B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 70B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 71B Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 72B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2,6-di-F 73B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-F.
  • 74B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Cl.
  • 75B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Br.
  • 76B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Me.
  • 77B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 78B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 79B Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2,6-di-Cl.
  • 80B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 81B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-F.
  • 82B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Cl.
  • 83B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Br.
  • 84B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Me.
  • 85B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 86B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 87B Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 88B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 89B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-F.
  • 90B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl.
  • 91B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Br.
  • 92B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Me.
  • 93B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 94B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 95B Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 96B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 97B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-F.
  • 98B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Cl.
  • 99B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Br.
  • 100B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Me 101B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 102B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 103B Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 104B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 105B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-F.
  • 106B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl.
  • 107B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Br.
  • 108B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Me.
  • 109B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 110B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 111B Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 112B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 113B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-F.
  • 114B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 115B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Br.
  • 116B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Me.
  • 117B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl 118B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 119B Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2,6-di-Cl.
  • 120B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 121B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-F.
  • 122B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 123B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Br.
  • 124B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Me.
  • 125B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 126B Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 127B Q 2 is 2,6-di-Br-4-Me—Ph
  • (R 3a ) p is 2,6-di-Cl.
  • 128B Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2,6-di-F.
  • 129B Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2-F.
  • 130B Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2-Cl.
  • 131B Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Br.
  • 132B Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Me.
  • 133B Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 134B Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 135B Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 136B Q 2 is 2-Cl-4-F, (R 3a ) p is 2,6-di-F.
  • 137B Q 2 is 2-Cl-4-F, (R 3a ) p is 2-F.
  • 138B Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Cl.
  • 139B Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Br.
  • 140B Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Me.
  • 141B Q 2 is 2-Cl-4-F, (R 3a ) p is 2-F, 6-Cl 142B Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Cl, 6-F 143B Q 2 is 2-Cl-4-F, (R 3a ) p is 2,6-di-Cl.
  • 144B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2,6-di-F.
  • 145B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-F.
  • 146B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Cl.
  • 147B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Br.
  • 148B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Me.
  • 149B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-F, 6-Cl.
  • 150B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Cl, 6-F.
  • 151B Q 2 is 2-Cl-4-Me, (R 3a ) p is 2,6-di-Cl.
  • 152B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2,6-di-F.
  • 153B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-F
  • 154B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Cl.
  • 155B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Br.
  • 156B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Me . . . 157B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-F, 6-Cl. 158B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Cl, 6-F. 159B Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2,6-di-Cl. 160B Q 2 is 2-Br-4-F, (R 3a ) p is 2,6-di-F. 161B Q 2 is 2-Br-4-F, (R 3a ) p is 2-F.
  • 162B Q 2 is 2-Br-4-F, (R 3a ) p is 2-Cl.
  • 163B Q 2 is 2-Br-4-F, (R 3a ) p is 2-Br.
  • 164B Q 2 is 2-Br-4-F, (R 3a ) p is 2-Me.
  • 165B Q 2 is 2-Br-4-F, (R 3a ) p is 2-F, 6-Cl.
  • 166B Q 2 is 2-Br-4-F, (R 3a ) p is 2-Cl, 6-F.
  • 167B Q 2 is 2-Br-4-F, (R 3a ) p is 2,6-di-Cl.
  • 168B Q 2 is 2-Br-4-Me, (R 3a ) p is 2,6-di-F.
  • 169B Q 2 is 2-Br-4-Me, (R 3a ) p is 2-F.
  • 170B Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Cl.
  • 171B Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Br.
  • 172B Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Me.
  • 173B Q 2 is 2-Br-4-Me, (R 3a ) p is 2-F, 6-Cl.
  • 174B Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Cl, 6-F.
  • 175B Q 2 is 2-Br-4-Me, (R 3a ) p is 2,6-di-Cl.
  • 176B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2,6-di-F.
  • 177B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-F.
  • 178B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Cl.
  • 179B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Br.
  • 180B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Me.
  • 181B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-F, 6-Cl.
  • 182B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Cl, 6-F.
  • 183B Q 2 is 2-Br-4-MeO, (R 3a ) p is 2,6-di-Cl.
  • 184B Q 2 is 2,4-di-Cl, (R 3a ) p is 2,6-di-F.
  • 185B Q 2 is 2,4-di-Cl, (R 3a ) p is 2-F.
  • 186B Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Cl.
  • 187B Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Br.
  • 188B Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Me.
  • 189B Q 2 is 2,4-di-Cl, (R 3a ) p is 2-F, 6-Cl.
  • 190B Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Cl, 6-F.
  • 191B Q 2 is 2,4-di-Cl, (R 3a ) p is 2,6-di-Cl.
  • 192B Q 2 is 2,6-di-Cl, (R 3a ) p is 2,6-di-F.
  • 193B Q 2 is 2,6-di-Cl, (R 3a ) p is 2-F.
  • 194B Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Cl.
  • 195B Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Br.
  • 196B Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Me.
  • 197B Q 2 is 2,6-di-Cl, (R 3a ) p is 2-F, 6-Cl.
  • 198B Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Cl, 6-F.
  • 199B Q 2 is 2,6-di-Cl, (R 3a ) p is 2,6-di-Cl.
  • 200B Q 2 is 2,4-di-Me, (R 3a ) p is 2,6-di-F.
  • 201B Q 2 is 2,4-di-Me, (R 3a ) p is 2-F.
  • 202B Q 2 is 2,4-di-Me, (R 3a ) p is 2-Cl.
  • 203B Q 2 is 2,4-di-Me, (R 3a ) p is 2-Br.
  • 204B Q 2 is 2,4-di-Me, (R 3a ) p is 2-Me.
  • 205B Q 2 is 2,4-di-Me, (R 3a ) p is 2-F, 6-Cl.
  • 206B Q 2 is 2,4-di-Me, (R 3a ) p is 2-Cl, 6-F.
  • 207B Q 2 is 2,4-di-Me, (R 3a ) p is 2,6-di-Cl.
  • 208B Q 2 is 2,6-di-Me, (R 3a ) p is 2,6-di-F.
  • 209B Q 2 is 2,6-di-Me, (R 3a ) p is 2-F.
  • 210B Q 2 is 2,6-di-Me, (R 3a ) p is 2-Cl 211B Q 2 is 2,6-di-Me, (R 3a ) p is 2-Br. 212B Q 2 is 2,6-di-Me, (R 3a ) p is 2-Me. 213B Q 2 is 2,6-di-Me, (R 3a ) p is 2-F, 6-Cl. 214B Q 2 is 2,6-di-Me, (R 3a ) p is 2-Cl, 6-F. 215B Q 2 is 2,6-di-Me, (R 3a ) p is 2,6-di-Cl.
  • the present disclosure also includes Tables 1C through 215C, each of which is constructed the same as Table 3 above, except that the row heading in Table 3 (i.e. “Q 2 is 2,4,6-tri-F-Ph, (R 3a ) p is 2,6-di-F”) is replaced with the respective row headings shown below.
  • Table 1C the row heading is “Q 2 is 2,4,6-tri-F-Ph, (R 3a ) p is 2-F”, and R 3b is as defined in Table 3 above.
  • Table 1C specifically discloses 5-[2-fluoro-4-(-propyn-1-yloxy)phenyl]-1,3-dimethyl-4-[(2,4,6-trifluorophenyl)-methyl]-1H-pyrazole.
  • Tables 2C through 215C are constructed similarly.
  • Table Row Heading 1C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-F.
  • 2C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Cl.
  • 3C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Br.
  • 4C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Me.
  • 5C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 6C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 7C Q 2 is 2,4,6-tri-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 8C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2,6-di-F.
  • 9C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-F.
  • 10C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-Cl.
  • 11C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-Br.
  • 12C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-Me.
  • 13C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 14C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 15C Q 2 is 2,6-di-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 16C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2,6-di-F.
  • 17C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-F.
  • 18C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Cl.
  • 19C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Br.
  • 20C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Me.
  • 21C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 22C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 23C Q 2 is 2,6-di-F-4-MeO—Ph, (R 3a ) p is 2,6-di-Cl.
  • 24C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 25C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-F.
  • 26C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 27C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Br.
  • 28C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Me.
  • 29C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl 30C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 31C Q 2 is 2,6-di-F-4-Me—Ph, (R 3a ) p is 2,6-di-Cl.
  • 32C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2,6-di-F.
  • 33C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-F.
  • 34C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Cl.
  • 35C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Br.
  • 36C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Me.
  • 37C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 38C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 39C Q 2 is 2,6-di-F-4-CN—Ph, (R 3a ) p is 2,6-di-Cl.
  • 40C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2,6-di-F.
  • 41C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-F.
  • 42C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Cl.
  • 43C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Br. 44C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Me. 45C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-F, 6-Cl. 46C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2-Cl, 6-F. 47C Q 2 is 2,6-di-F-4-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 53C Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 54C Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 55C Q 2 is 2,6-di-F-4-Br—Ph, (R 3a ) p is 2,6-di-Cl.
  • 56C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2,6-di-F.
  • 57C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-F.
  • 58C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Cl.
  • 59C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Br.
  • 60C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Me
  • 61C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 62C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 63C Q 2 is 2,4-di-F—Ph, (R 3a ) p is 2,6-di-Cl 64C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2,6-di-F.
  • 65C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-F.
  • 66C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Cl.
  • 67C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Br.
  • 68C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Me.
  • 69C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 70C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 71C Q 2 is 2,4-di-F-6-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 72C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2,6-di-F 73C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-F.
  • 74C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Cl.
  • 75C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Br.
  • 76C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Me.
  • 77C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 78C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 79C Q 2 is 2,4-di-F-6-Br—Ph, (R 3a ) p is 2,6-di-Cl.
  • 80C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 81C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-F.
  • 82C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Cl.
  • 83C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Br.
  • 84C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Me.
  • 85C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 86C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 87C Q 2 is 2-Cl-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 88C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 89C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-F.
  • 90C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl.
  • 91C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Br.
  • 92C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Me.
  • 93C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 94C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 95C Q 2 is 2-Cl-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 96C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 97C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-F.
  • 98C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Cl.
  • 99C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Br.
  • 100C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Me 101C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 102C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 103C Q 2 is 2-Br-4-Me-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 104C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-F.
  • 105C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-F.
  • 106C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl.
  • 107C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Br.
  • 108C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Me.
  • 109C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 110C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 111C Q 2 is 2-Br-4-MeO-6-F—Ph, (R 3a ) p is 2,6-di-Cl.
  • 112C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 113C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-F.
  • 114C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 115C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Br.
  • 116C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Me.
  • 117C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl 118C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 119C Q 2 is 2,6-di-Cl-4-Me—Ph, (R 3a ) p is 2,6-di-Cl.
  • 120C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2,6-di-F.
  • 121C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-F.
  • 122C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Cl.
  • 123C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Br.
  • 124C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Me.
  • 125C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 126C Q 2 is 2,6-di-Br-4-Me—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 127C Q 2 is 2,6-di-Br-4-Me—Ph
  • (R 3a ) p is 2,6-di-Cl.
  • 128C Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2,6-di-F.
  • 129C Q 2 is 2,4,6-tri-Cl—Ph
  • (R 3a ) p is 2-F.
  • 130C Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Cl.
  • 131C Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Br.
  • 132C Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Me.
  • 133C Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-F, 6-Cl.
  • 134C Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2-Cl, 6-F.
  • 135C Q 2 is 2,4,6-tri-Cl—Ph, (R 3a ) p is 2,6-di-Cl.
  • 136C Q 2 is 2-Cl-4-F, (R 3a ) p is 2,6-di-F.
  • 137C Q 2 is 2-Cl-4-F, (R 3a ) p is 2-F.
  • 138C Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Cl.
  • 139C Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Br.
  • 140C Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Me.
  • 141C Q 2 is 2-Cl-4-F, (R 3a ) p is 2-F, 6-Cl 142C Q 2 is 2-Cl-4-F, (R 3a ) p is 2-Cl, 6-F 143C Q 2 is 2-Cl-4-F, (R 3a ) p is 2,6-di-Cl.
  • 144C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2,6-di-F.
  • 145C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-F.
  • 146C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Cl.
  • 147C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Br.
  • 148C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Me.
  • 149C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-F, 6-Cl.
  • 150C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2-Cl, 6-F.
  • 151C Q 2 is 2-Cl-4-Me, (R 3a ) p is 2,6-di-Cl.
  • 152C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2,6-di-F.
  • 153C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-F
  • 154C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Cl.
  • 155C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Br.
  • 156C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Me . . . 157C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-F, 6-Cl. 158C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2-Cl, 6-F. 159C Q 2 is 2-Cl-4-MeO, (R 3a ) p is 2,6-di-Cl. 160C Q 2 is 2-Br-4-F, (R 3a ) p is 2,6-di-F. 161C Q 2 is 2-Br-4-F, (R 3a ) p is 2-F.
  • 162C Q 2 is 2-Br-4-F, (R 3a ) p is 2-Cl.
  • 163C Q 2 is 2-Br-4-F, (R 3a ) p is 2-Br.
  • 164C Q 2 is 2-Br-4-F, (R 3a ) p is 2-Me.
  • 165C Q 2 is 2-Br-4-F, (R 3a ) p is 2-F, 6-Cl.
  • 166C Q 2 is 2-Br-4-F, (R 3a ) p is 2-Cl, 6-F.
  • 167C Q 2 is 2-Br-4-F, (R 3a ) p is 2,6-di-Cl.
  • 168C Q 2 is 2-Br-4-Me, (R 3a ) p is 2,6-di-F.
  • 169C Q 2 is 2-Br-4-Me, (R 3a ) p is 2-F.
  • 170C Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Cl.
  • 171C Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Br.
  • 172C Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Me.
  • 173C Q 2 is 2-Br-4-Me, (R 3a ) p is 2-F, 6-Cl.
  • 174C Q 2 is 2-Br-4-Me, (R 3a ) p is 2-Cl, 6-F. 175C Q 2 is 2-Br-4-Me, (R 3a ) p is 2,6-di-Cl.
  • 176C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2,6-di-F.
  • 177C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-F.
  • 178C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Cl.
  • 179C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Br.
  • 180C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Me.
  • 181C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-F, 6-Cl.
  • 182C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2-Cl, 6-F.
  • 183C Q 2 is 2-Br-4-MeO, (R 3a ) p is 2,6-di-Cl.
  • 184C Q 2 is 2,4-di-Cl, (R 3a ) p is 2,6-di-F.
  • 185C Q 2 is 2,4-di-Cl, (R 3a ) p is 2-F.
  • 186C Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Cl.
  • 187C Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Br.
  • 188C Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Me.
  • 189C Q 2 is 2,4-di-Cl, (R 3a ) p is 2-F, 6-Cl.
  • 190C Q 2 is 2,4-di-Cl, (R 3a ) p is 2-Cl, 6-F.
  • 191C Q 2 is 2,4-di-Cl, (R 3a ) p is 2,6-di-Cl.
  • 192C Q 2 is 2,6-di-Cl, (R 3a ) p is 2,6-di-F.
  • 193C Q 2 is 2,6-di-Cl, (R 3a ) p is 2-F.
  • 194C Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Cl.
  • 195C Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Br.
  • 196C Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Me.
  • 197C Q 2 is 2,6-di-Cl, (R 3a ) p is 2-F, 6-Cl.
  • 198C Q 2 is 2,6-di-Cl, (R 3a ) p is 2-Cl, 6-F.
  • 199C Q 2 is 2,6-di-Cl, (R 3a ) p is 2,6-di-Cl.
  • 200C Q 2 is 2,4-di-Me, (R 3a ) p is 2,6-di-F.
  • 201C Q 2 is 2,4-di-Me, (R 3a ) p is 2-F.
  • 202C Q 2 is 2,4-di-Me, (R 3a ) p is 2-Cl.
  • 203C Q 2 is 2,4-di-Me, (R 3a ) p is 2-Br.
  • 204C Q 2 is 2,4-di-Me, (R 3a ) p is 2-Me.
  • 205C Q 2 is 2,4-di-Me, (R 3a ) p is 2-F, 6-Cl.
  • 206C Q 2 is 2,4-di-Me, (R 3a ) p is 2-Cl, 6-F.
  • 207C Q 2 is 2,4-di-Me, (R 3a ) p is 2,6-di-Cl.
  • 208C Q 2 is 2,6-di-Me, (R 3a ) p is 2,6-di-F.
  • 209C Q 2 is 2,6-di-Me, (R 3a ) p is 2-F.
  • 210C Q 2 is 2,6-di-Me, (R 3a ) p is 2-Cl 211C Q 2 is 2,6-di-Me, (R 3a ) p is 2-Br.
  • 212C Q 2 is 2,6-di-Me, (R 3a ) p is 2-Me.
  • 213C Q 2 is 2,6-di-Me, (R 3a ) p is 2-F, 6-Cl.
  • 214C Q 2 is 2,6-di-Me, (R 3a ) p is 2-Cl, 6-F.
  • 215C Q 2 is 2,6-di-Me, (R 3a ) p is 2,6-di-Cl.
  • a compound of this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier.
  • a composition i.e. formulation
  • additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier.
  • the formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
  • Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels.
  • aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion.
  • nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
  • the general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible (“wettable”) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment.
  • Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or “overcoated”). Encapsulation can control or delay release of the active ingredient.
  • An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.
  • Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
  • the formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
  • Weight Percent Active Ingredient Diluent Surfactant Water-Dispersible and Water- 0.001-90 0-99.999 0-15 soluble Granules, Tablets and Powders Oil Dispersions, Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including Emulsifiable Concentrates) Dusts 1-25 70-99 0-5 Granules and Pellets 0.001-95 5-99.999 0-15 High Strength Compositions 90-99 0-10 0-2
  • Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate.
  • Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, N.J.
  • Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentan
  • Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C 6 -C 22 ), such as plant seed and fruit oils (e.g., oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof.
  • plant seed and fruit oils e.g., oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel
  • animal-sourced fats e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil
  • Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation.
  • alkylated fatty acids e.g., methylated, ethylated, butylated
  • Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
  • the solid and liquid compositions of the present invention often include one or more surfactants.
  • surfactants also known as “surface-active agents”
  • surface-active agents generally modify, most often reduce, the surface tension of the liquid.
  • surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.
  • Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene
  • Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of e
  • Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
  • amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amine
  • Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon's Emulsifiers and Detergents , annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents , Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents , Seventh Edition, John Wiley and Sons, New York, 1987.
  • compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants).
  • formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes.
  • Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes.
  • formulation auxiliaries and additives include those listed in McCutcheon's Volume 2 : Functional Materials , annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
  • the compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent.
  • Solutions, including emulsifiable concentrates can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water.
  • Active ingredient slurries, with particle diameters of up to 2,000 ⁇ m can be wet milled using media mills to obtain particles with average diameters below 3 ⁇ m.
  • Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. Pat. No. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 ⁇ m range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, “Agglomeration”, Chemical Engineering , Dec.
  • Pellets can be prepared as described in U.S. Pat. No. 4,172,714.
  • Water-dispersible and water-soluble granules can be prepared as taught in U.S. Pat. No. 4,144,050, U.S. Pat. No. 3,920,442 and DE 3,246,493.
  • Tablets can be prepared as taught in U.S. Pat. No. 5,180,587, U.S. Pat. No. 5,232,701 and U.S. Pat. No. 5,208,030.
  • Films can be prepared as taught in GB 2,095,558 and U.S. Pat. No. 3,299,566.
  • Compound 2 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
  • Compound 2 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0% U.S.S. No. 25-50 sieves)
  • Compound 2 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%
  • Compound 2 10.0% polyoxyethylene sorbitol hexoleate 20.0% C 6 -C 10 fatty acid methyl ester 70.0%
  • Compound 2 20.00% polyvinylpyrrolidone-vinyl acetate copolymer 5.00% montan acid wax 5.00% calcium ligninsulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% colorant red dye 0.05% water 65.75%
  • Water-soluble and water-dispersible formulations are typically diluted with water to form aqueous compositions before application.
  • Aqueous compositions for direct applications to the plant or portion thereof typically at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.
  • the compounds of this invention are useful as plant disease control agents.
  • the present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound.
  • the compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops.
  • pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum , and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica ), Pseudoperonospora spp.
  • Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici
  • Pythium diseases such as Pythium aphanidermatum
  • diseases in the Peronosporaceae family
  • Ascomycetes including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici , powdery mildew diseases such as Erysiphe spp.
  • Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Sclerotinia minor, Magnaporthe grisea , and Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis and Pyrenophora teres , anthracnose diseases such as Glomerella or Colletotrichum spp.
  • Puccinia spp. such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis ), Hemileia vastatrix and Phakopsora pachyrhizi ; other pathogens including Rutstroemia floccosum (also known as Sclerotinia homoeocarpa ); Rhizoctonia spp.
  • Rhizoctonia solani Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; Rhizopus spp. (such as Rhizopus stolonifer ); Aspergillus spp. (such as Aspergillus flavus and Aspergillus parasiticus ); and other genera and species closely related to these pathogens.
  • compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae , and other related species.
  • bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae , and other related species.
  • the compounds of this invention are useful in treating postharvest diseases of fruits and vegetables caused by fungi and bacteria. These infections can occur before, during and after harvest. For example, infections can occur before harvest and then remain dormant until some point during ripening (e.g., host begins tissue changes in such a way that infection can progress); also infections can arise from surface wounds created by mechanical or insect injury. In this respect, the compounds of this invention can reduce losses (i.e.
  • Treatment of postharvest diseases with compounds of the invention can increase the period of time during which perishable edible plant parts (e.g, fruits, seeds, foliage, stems, bulbs, tubers) can be stored refrigerated or un-refrigerated after harvest, and remain edible and free from noticeable or harmful degradation or contamination by fungi or other microorganisms.
  • Treatment of edible plant parts before or after harvest with compounds of the invention can also decrease the formation of toxic metabolites of fungi or other microorganisms, for example, mycotoxins such as aflatoxins.
  • Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruits, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing.
  • the compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds.
  • the compounds can also be applied through irrigation water to treat plants. Control of postharvest pathogens which infect the produce before harvest is typically accomplished by field application of a compound of this invention, and in cases where infection occurs after harvest the compounds can be applied to the harvested crop as dips, sprays, fumigants, treated wraps and box liners.
  • Rates of application for these compounds can be influenced by factors such as the plant diseases to be controlled, the plant species to be protected, ambient moisture and temperature and should be determined under actual use conditions.
  • a fungicidally effective amount can be influenced by factors such as the plant diseases to be controlled, the plant species to be protected, ambient moisture and temperature and should be determined under actual use conditions.
  • One skilled in the art can easily determine through simple experimentation the fungicidally effective amount necessary for the desired level of plant disease control.
  • Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredient.
  • Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 10 g per kilogram of seed.
  • Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection.
  • fungicides insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners
  • growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus
  • the present invention also pertains to a composition
  • a composition comprising a compound of Formula 1 (in a fungicidally effective amount) and at least one additional biologically active compound or agent (in a biologically effective amount) and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent.
  • the other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent.
  • one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
  • compositions which in addition to the compound of Formula 1 include at least one fungicidal compound selected from the group consisting of the classes (1) methyl benzimidazole carbamate (MBC) fungicides; (2) dicarboximide fungicides; (3) demethylation inhibitor (DMI) fungicides; (4) phenylamide fungicides; (5) amine/morpholine fungicides; (6) phospholipid biosynthesis inhibitor fungicides; (7) carboxamide fungicides; (8) hydroxy(2-amino-)pyrimidine fungicides; (9) anilinopyrimidine fungicides; (10) N-phenyl carbamate fungicides; (11) quinone outside inhibitor (QoI) fungicides; (12) phenylpyrrole fungicides; (13) quinoline fungicides; (14) lipid peroxidation inhibitor fungicides; (15) melanin biosynthesis inhibitors-reductase (MBI-R) fungicides; (15)
  • Methyl benzimidazole carbamate (MBC) fungicides (Fungicide Resistance Action Committee (FRAC) code 1) inhibit mitosis by binding to ⁇ -tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure.
  • Methyl benzimidazole carbamate fungicides include benzimidazoles and thiophanates.
  • the benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole.
  • the thiophanates include thiophanate and thiophanate-methyl.
  • Demethylation inhibitor (DMI) fungicides (Fungicide Resistance Action Committee (FRAC) code 3) inhibit C14-demethylase, which plays a role in sterol production.
  • Sterols such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi.
  • Demethylation fungicides include piperazines, pyridines, pyrimidines, imidazoles and triazoles.
  • the piperazines include triforine.
  • the pyridines include buthiobate and pyrifenox.
  • the pyrimidines include fenarimol, nuarimol and triarimol.
  • the imidazoles include clotrimazole, imazalil, oxpoconazole, prochloraz, pefurazoate and triflumizole.
  • the triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, 1-[[
  • the imidazoles include clotrimazole, imazalil, oxpoconazole, prochloraz, pefurazoate and triflumizole.
  • Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides—Properties, Applications and Mechanisms of Action , H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
  • Phenylamide fungicides are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide.
  • Phenylamide fungicides include acylalanines, oxazolidinones and butyrolactones.
  • the acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl and metalaxyl-M/mefenoxam.
  • the oxazolidinones include oxadixyl.
  • the butyrolactones include ofurace.
  • Amine/morpholine fungicides include morpholines, piperidines and spiroketal-amines.
  • the morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide.
  • the piperidines include fenpropidin and piperalin.
  • the spiroketal-amines include spiroxamine.
  • Phospholipid biosynthesis inhibitor fungicides include phophorothiolates and dithiolanes.
  • the phosphorothiolates include edifenphos, iprobenfos and pyrazophos.
  • the dithiolanes include isoprothiolane.
  • Carboxamide fungicides (Fungicide Resistance Action Committee (FRAC) code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction.
  • Carboxamide fungicides include phenyl benzamides, pyridinyl ethyl benzamides, furan carboxamides, oxathiin carboxamides, thiazole carboxamides, pyrazole carboxamides and pyridine carboxamides.
  • the phenyl benzamides include benodanil, flutolanil and mepronil.
  • the pyridinyl ethyl benzamides include fluopyram.
  • the furan carboxamides include fenfuram.
  • the oxathiin carboxamides include carboxin and oxycarboxin.
  • the thiazole carboxamides include thifluzamide.
  • the pyrazole carboxamides include furametpyr, penthiopyrad, bixafen, isopyrazam, benzovindiflupyr, N-[2-(1S,2R)-[1,1′-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, penflufen, (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide), N-[2-(2,4-dichlorophenyl)-2-methoxy-1-methylethyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[[2-(1-methylethyl)phenyl]methyl]-1H-pyrazole-4
  • “Hydroxy(2-amino-)pyrimidine fungicides” (Fungicide Resistance Action Committee (FRAC) code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.
  • Anilinopyrimidine fungicides (Fungicide Resistance Action Committee (FRAC) code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
  • N-Phenyl carbamate fungicides (Fungicide Resistance Action Committee (FRAC) code 10) inhibit mitosis by binding to ⁇ -tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
  • QoI Quinone outside inhibitor
  • FRAC Field Resistance Action Committee
  • Quinone outside inhibitor fungicides include methoxyacrylates, methoxycarbamates, oximinoacetates, oximinoacetamides, oxazolidinediones, dihydrodioxazines, imidazolinones and benzylcarbamates.
  • the methoxyacrylates include azoxystrobin, coumoxystrobin, enestroburin, flufenoxystrobin, picoxystrobin and pyraoxystrobin.
  • the methoxycarbamates include pyraclostrobin, pyrametostrobin and triclopyricarb.
  • the oximinoacetates include kresoxim-methyl and trifloxystrobin.
  • the oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin, ⁇ -[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]-methyl]benzeneacetamide and 2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]-amino]oxy]methyl]- ⁇ -(methoxyimino)-N-methylbenzeneacetamide.
  • the oxazolidinediones include famoxadone.
  • the dihydrodioxazines include fluoxastrobin.
  • the imidazolinones include fenamidone.
  • the benzylcarbamates include pyribencarb.
  • Class (11) also includes 2-[(2,5-dimethylphenoxy)methyl]- ⁇ -methoxy-N-benzeneacetamide.
  • Azanaphthalene fungicides (Fungicide Resistance Action Committee (FRAC) code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases.
  • Azanaphthalene fungicides include aryloxyquinolines and quinazolinone.
  • the aryloxyquinolines include quinoxyfen and tebufloquin.
  • the quinazolinones include proquinazid.
  • Lipid peroxidation inhibitor fungicides are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis.
  • Lipid peroxidation fungicides include aromatic carbons and 1,2,4-thiadiazoles.
  • the aromatic carbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl.
  • the 1,2,4-thiadiazole fungicides include etridiazole.
  • MMI-R Melanin biosynthesis inhibitors-reductase fungicides
  • FRAC Field Action Committee
  • MBI-D Melanin biosynthesis inhibitors-dehydratase fungicides
  • FRAC Field Action Committee
  • scytalone dehydratase in melanin biosynthesis Melanin in required for host plant infection by some fungi.
  • Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamides, carboxamides and propionamides.
  • the cyclopropanecarboxamides include carpropamid.
  • the carboxamides include diclocymet.
  • the propionamides include fenoxanil.
  • Squalene-epoxidase inhibitor fungicides include thiocarbamates and allylaminess.
  • the thiocarbamates include pyributicarb.
  • the allylamines include naftifine and terbinafine.
  • Polyoxin fungicides (Fungicide Resistance Action Committee (FRAC) code 19) inhibit chitin synthase. Examples include polyoxin.
  • Quinone inside inhibitor (QiI) fungicides (Fungicide Resistance Action Committee (FRAC) code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the “quinone inside” (Q i ) site of the cytochrome bc 1 complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development.
  • Quinone inside inhibitor fungicides include cyanoimidazoles and sulfamoyltriazoles.
  • the cyanoimidazoles include cyazofamid.
  • the sulfamoyltriazoles include amisulbrom.
  • Benzamide fungicides (Fungicide Resistance Action Committee (FRAC) code 22) inhibit mitosis by binding to ⁇ -tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.
  • Endopyranuronic acid antibiotic fungicides (Fungicide Resistance Action Committee (FRAC) code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.
  • Halopyranosyl antibiotic fungicides (Fungicide Resistance Action Committee (FRAC) code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin.
  • Glucopyranosyl antibiotic protein synthesis fungicides
  • FRAC Field Resistance Action Committee
  • “Cyanoacetamideoxime fungicides (Fungicide Resistance Action Committee (FRAC) code 27) include cymoxanil.
  • “Carbamate fungicides” (Fungicide Resistance Action Committee (FRAC) code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, propamacarb-hydrochloride, iodocarb, and prothiocarb are examples of this fungicide class.
  • Oxidative phosphorylation uncoupling fungicides (Fungicide Resistance Action Committee (FRAC) code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development.
  • This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
  • Carboxylic acid fungicides (Fungicide Resistance Action Committee (FRAC) code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
  • Heteroaromatic fungicides Fungicide Resistance Action Committee (FRAC) code 32
  • FRAC Fungicide Resistance Action Committee
  • Heteroaromatic fungicides include isoxazoles and isothiazolones.
  • the isoxazoles include hymexazole and the isothiazolones include octhilinone.
  • Phosphonate fungicides include phosphorous acid and its various salts, including fosetyl-aluminum.
  • Phthalamic acid fungicides include teclofthalam.
  • Thiophene-carboxamide fungicides (Fungicide Resistance Action Committee (FRAC) code 38) are proposed to affect ATP production. Examples include silthiofam.
  • “Pyrimidinamide fungicides” (Fungicide Resistance Action Committee (FRAC) code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
  • Carboxylic acid amide (CAA) fungicides are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus.
  • Carboxylic acid amide fungicides include cinnamic acid amides, valinamide carbamates, carbamates and mandelic acid amides.
  • the cinnamic acid amides include dimethomorph and flumorph.
  • the valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb, valifenalate and valiphenal.
  • the carbamates include tolprocarb.
  • the mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)-amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]-ethyl]-3-methyl-2-[(ethyl sulfonyl)amino]butanamide.
  • “Tetracycline antibiotic fungicides” (Fungicide Resistance Action Committee (FRAC) code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline.
  • Thiocarbamate fungicides include methasulfocarb.
  • Benzamide fungicides (Fungicide Resistance Action Committee (FRAC) code 43) inhibit growth of fungi by delocalization of spectrin-like proteins.
  • Examples include acylpicolide fungicides such as fluopicolide.
  • Host plant defense induction fungicides include benzothiadiazoles, benzisothiazoles and thiadiazolecarboxamides.
  • the benzothiadiazoles include acibenzolar-S-methyl.
  • the benzisothiazoles include probenazole.
  • the thiadiazolecarboxamides include tiadinil and isotianil.
  • Multi-site contact fungicides inhibit fungal growth through multiple sites of action and have contact/preventive activity.
  • This class of fungicides includes: (45.1) “copper fungicides” (Fungicide Resistance Action Committee (FRAC) code M1)”, (45.2) “sulfur fungicides” (Fungicide Resistance Action Committee (FRAC) code M2), (45.3) “dithiocarbamate fungicides” (Fungicide Resistance Action Committee (FRAC) code M3), (45.4) “phthalimide fungicides” (Fungicide Resistance Action Committee (FRAC) code M4), (45.5) “chloronitrile fungicides” (Fungicide Resistance Action Committee (FRAC) code M5), (45.6) “sulfamide fungicides” (Fungicide Resistance Action Committee (FRAC) code M6), (45.7) “guanidine fungicides” (Fungicide Resistance Action Committee (FRAC) code M7), (45.8) “triazine fungicides” (Fungicide Resistance Action Committee
  • Copper fungicides are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate).
  • Sulfur fungicides are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur.
  • Dithiocarbamate fungicides contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram.
  • Phthalimide fungicides contain a phthalimide molecular moiety; examples include folpet, captan and captafol. “Chloronitrile fungicides” contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. “Sulfamide fungicides” include dichlofluanid and tolyfluanid. “Guanidine fungicides” include dodine, guazatine, iminoctadine albesilate and iminoctadine triacetate. “Triazine fungicides” include anilazine. “Quinone fungicides” include dithianon.
  • “Fungicides other than fungicides of classes (1) through (45)” include certain fungicides whose mode of action may be unknown. These include: (46.1) “thiazole carboxamide fungicides” (Fungicide Resistance Action Committee (FRAC) code U5), (46.2) “phenylacetamide fungicides” (Fungicide Resistance Action Committee (FRAC) code U6), (46.3) “arylphenylketone fungicides” (Fungicide Resistance Action Committee (FRAC) code U8) and (46.4) “triazolopyrimidine fungicides”.
  • the thiazole carboxamides include ethaboxam.
  • the phenylacetamides include cyflufenamid and N-[[(cyclopropylmethoxy)-amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide.
  • the arylphenylketones include benzophenones such as metrafenone and benzoylpyridines such as pyriofenone.
  • the triazolopyrimidines include ametoctradin. Class (46) (i.e.
  • “Fungicides other than classes (1) through (45)”) also includes bethoxazin, fluxapyroxad, neo-asozin (ferric methanearsonate), pyrrolnitrin, quinomethionate, tebufloquin, isofetamid, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methyl sulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethyl sulfonyl)amino]butanamide, 2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-
  • a mixture comprising a compound of Formula 1 and at least one fungicidal compound selected from the group consisting of the aforedescribed classes (1) through (46).
  • a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • a mixture comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (1) through (46).
  • a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • insecticides such as abamectin, acephate, acetamiprid, acrinathrin, amidoflumet (S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyflumetofen, cyfluthrin, beta-cy
  • Bacillus thuringiensis subsp. kurstaki , and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as CpGV.
  • NPV nucleopolyhedro virus
  • GV granulosis virus
  • Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins).
  • proteins toxic to invertebrate pests such as Bacillus thuringiensis delta-endotoxins.
  • the effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins.
  • the weight ratio of these various mixing partners (in total) to the compound of Formula 1 is typically between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (for example ratios between about 1:30 and about 30:1).
  • weight ratios between about 1:300 and about 300:1 for example ratios between about 1:30 and about 30:1.
  • One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.
  • combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable.
  • synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
  • a combination of a compound of Formula 1 with at least one other fungicidal active ingredient is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1.
  • a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management.
  • a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.
  • compositions which in addition to compound of Formula 1 include at least one compound selected from the group consisting of (1) alkylenebis(dithiocarbamate) fungicides; (2) cymoxanil; (3) phenylamide fungicides; (4) proquinazid (6-iodo-3-propyl-2-propyloxy-4(3H)-quinazolinone); (5) chlorothalonil; (6) carboxamides acting at complex II of the fungal mitochondrial respiratory electron transfer site; (7) quinoxyfen; (8) metrafenone; (9) cyflufenamid; (10) cyprodinil; (11) copper compounds; (12) phthalimide fungicides; (13) fosetyl-aluminum; (14) benzimidazole fungicides; (15) cyazofamid; (16) fluazinam; (17) iprovalicarb; (18) propamocarb; (19) validomycin; (20) dichloroph
  • Sterol biosynthesis inhibitors control fungi by inhibiting enzymes in the sterol biosynthesis pathway.
  • Demethylase-inhibiting fungicides have a common site of action within the fungal sterol biosynthesis pathway, involving inhibition of demethylation at position 14 of lanosterol or 24-methylene dihydrolanosterol, which are precursors to sterols in fungi. Compounds acting at this site are often referred to as demethylase inhibitors, DMI fungicides, or DMIs.
  • the demethylase enzyme is sometimes referred to by other names in the biochemical literature, including cytochrome P-450 (14DM). The demethylase enzyme is described in, for example, J. Biol. Chem.
  • DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines.
  • the triazoles include azaconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and unicon
  • the imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz and triflumizole.
  • the pyrimidines include fenarimol, nuarimol and triarimol.
  • the piperazines include triforine.
  • the pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action , H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
  • bc 1 Complex Fungicides (group 28) have a fungicidal mode of action which inhibits the bc 1 complex in the mitochondrial respiration chain.
  • the bc 1 complex is sometimes referred to by other names in the biochemical literature, including complex III of the electron transfer chain, and ubihydroquinone:cytochrome c oxidoreductase. This complex is uniquely identified by Enzyme Commission number EC1.10.2.2.
  • the bc 1 complex is described in, for example, J. Biol. Chem. 1989, 264, 14543-48 ; Methods Enzymol. 1986, 126, 253-71; and references cited therein.
  • Strobilurin fungicides such as azoxystrobin, dimoxystrobin, enestroburin (SYP-Z071), fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin, pyraoxystrobin and trifloxystrobin are known to have this mode of action (H. Sauter et al., Angew. Chem. Int. Ed. 1999, 38, 1328-1349).
  • Other fungicidal compounds that inhibit the bc 1 complex in the mitochondrial respiration chain include famoxadone and fenamidone.
  • Alkylenebis(dithiocarbamate)s include compounds such as mancozeb, maneb, propineb and zineb.
  • Phenylamides (group (3)) include compounds such as metalaxyl, benalaxyl, furalaxyl and oxadixyl.
  • Carboxamides include compounds such as boscalid, carboxin, fenfuram, flutolanil, furametpyr, mepronil, oxycarboxin, thifluzamide, penthiopyrad and N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149), and are known to inhibit mitochondrial function by disrupting complex II (succinate dehydrogenase) in the respiratory electron transport chain.
  • complex II succinate dehydrogenase
  • Copper compounds include compounds such as copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate).
  • Phthalimides include compounds such as folpet and captan.
  • Benzimidazole fungicides include benomyl and carbendazim.
  • Dichlorophenyl dicarboximide fungicides include chlozolinate, dichlozoline, iprodione, isovaledione, myclozolin, procymidone and vinclozolin.
  • Non-DMI sterol biosynthesis inhibitors include morpholine and piperidine fungicides.
  • the morpholines and piperidines are sterol biosynthesis inhibitors that have been shown to inhibit steps in the sterol biosynthesis pathway at a point later than the inhibitions achieved by the DMI sterol biosynthesis (group (27)).
  • the morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide.
  • the piperidines include fenpropidin.
  • test suspensions for Tests A-E the test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-E. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of 800 g/ha.
  • test suspension was sprayed to the point of run-off on wheat seedlings.
  • seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 6 days, after which time visual disease ratings were made.
  • test suspension was sprayed to the point of run-off on wheat seedlings.
  • seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in a saturated atmosphere at 24° C. for 48 h, and then moved to a growth chamber at 20° C. for 19 days, after which time visual disease ratings were made.
  • test suspension was sprayed to the point of run-off on tomato seedlings.
  • seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis ) and incubated in a saturated atmosphere at 20° C. for 48 h, and then moved to a growth chamber at 24° C. for 3 days, after which time visual disease ratings were made.
  • Botrytis cinerea the causal agent of tomato Botrytis
  • test suspension was sprayed to the point of run-off on wheat seedlings.
  • seedlings were inoculated with a spore dust of Blumeria graminis f. sp. tritici , also known as Erysiphe graminis f. sp. tritici (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20° C. for 8 days, after which time visual disease ratings were made.
  • test suspension was sprayed to the point of run-off on wheat seedlings.
  • seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of Septoria glume blotch) and incubated in a saturated atmosphere at 24° C. for 48 h, and then moved to a growth chamber at 20° C. for 9 days, after which time visual disease ratings were made.
  • Septoria nodorum the causal agent of Septoria glume blotch
  • Results for Tests A-E are given in Table A. In the Table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). All results are for compounds tested at 200 ppm except where followed by an asterisk “*” which indicates the compound was tested at 250 ppm. A dash (-) indicates no test results.
  • Test B Test C Test D Test E 1 68 — 0 98 0 2 95 — 98 98 100 3 68 — 59 81 98 4 0 — 0 0 0 5 100 99 98 99 — 6 99 99 99 95 — 7 99 — 97 93 — 8 90 95 30 27 0 9 9 87 0 21* 0 10 99 96 12 94 100 11 86 98 15 69 0 12 89 95 97 73 0 13 0 98 0 98 — 14 100 99 39 95 — 15 98* 100* 98* 95* — 16 100* 100* 97* 99* — 17 100* 99* 69* 100* — 18 100* 99* 31* 99* — 19 100* 99* 100* 95* —

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